Resting-state functional magnetic resonance imaging has revealed disrupted brain network connectivity in adults and teenagers with cerebral palsy. However, the specific brain networks implicated in neonatal cases rema...Resting-state functional magnetic resonance imaging has revealed disrupted brain network connectivity in adults and teenagers with cerebral palsy. However, the specific brain networks implicated in neonatal cases remain poorly understood. In this study, we recruited 14 termborn infants with mild hypoxic ischemic encephalopathy and 14 term-born infants with severe hypoxic ischemic encephalopathy from Changzhou Children's Hospital, China. Resting-state functional magnetic resonance imaging data showed efficient small-world organization in whole-brain networks in both the mild and severe hypoxic ischemic encephalopathy groups. However, compared with the mild hypoxic ischemic encephalopathy group, the severe hypoxic ischemic encephalopathy group exhibited decreased local efficiency and a low clustering coefficient. The distribution of hub regions in the functional networks had fewer nodes in the severe hypoxic ischemic encephalopathy group compared with the mild hypoxic ischemic encephalopathy group. Moreover, nodal efficiency was reduced in the left rolandic operculum, left supramarginal gyrus, bilateral superior temporal gyrus, and right middle temporal gyrus. These results suggest that the topological structure of the resting state functional network in children with severe hypoxic ischemic encephalopathy is clearly distinct from that in children with mild hypoxic ischemic encephalopathy, and may be associated with impaired language, motion, and cognition. These data indicate that it may be possible to make early predictions regarding brain development in children with severe hypoxic ischemic encephalopathy, enabling early interventions targeting brain function. This study was approved by the Regional Ethics Review Boards of the Changzhou Children's Hospital(approval No. 2013-001) on January 31, 2013. Informed consent was obtained from the family members of the children. The trial was registered with the Chinese Clinical Trial Registry(registration number: ChiCTR1800016409) and the protocol version is 1.0.展开更多
Perinatal hypoxic-ischemic encephalopathy is a leading cause of neonatal death and disability.Therapeutic hypothermia significantly reduces death and major disability associated with hypoxic-ischemic encephalopathy;ho...Perinatal hypoxic-ischemic encephalopathy is a leading cause of neonatal death and disability.Therapeutic hypothermia significantly reduces death and major disability associated with hypoxic-ischemic encephalopathy;however,many infants still experience lifelong disabilities to movement,sensation and cognition.Clinical guidelines,based on strong clinical and preclinical evidence,recommend therapeutic hypothermia should be started within 6 hours of birth and continued for a period of 72 hours,with a target brain temperature of 33.5 ±0.5℃ for infants with moderate to severe hypoxic-ischemic encephalopathy.The clinical guidelines also recommend that infants be re warmed at a rate of 0.5℃ per hour,but this is not based on strong evidence.There are no randomized controlled trials investigating the optimal rate of rewarming after therapeutic hypothermia for infants with hypoxic-ischemic encephalopathy.Preclinical studies of rewarming are conflicting and results were confounded by treatment with sub-optimal durations of hypothermia.In this review,we evaluate the evidence for the optimal start time,duration and depth of hypothermia,and whether the rate of rewarming after treatment affects brain injury and neurological outcomes.展开更多
Neural stem cell transplantation is a useful treatment for ischemic stroke, but apoptosis often occurs in the hypoxic-ischemic environment of the brain after cell transplantation. In this study, we determined if mild ...Neural stem cell transplantation is a useful treatment for ischemic stroke, but apoptosis often occurs in the hypoxic-ischemic environment of the brain after cell transplantation. In this study, we determined if mild hypothermia （27-28~C） can increase the survival rate of neural stem cells （1.0 x 105/~tL） transplanted into neonatal mice with hypoxic-ischemic encephalopathy. Long-term effects on neurological functioning of the mice were also examined. After mild hy- pothermia combined with neural stem cell transplantation, we observed decreased expression levels of inflammatory factor nuclear factor-kappa B and apoptotic factor caspase-3, reduced cerebral infarct volumes, increased survival rate of transplanted cells, and marked improvements in neurological function. Thus, the neuroprotective effects of mild hypothermia combined with neural stem cell transplantation are superior to those of monotherapy. Moreover, our findings suggest that the neuroprotective effects of mild hypothermia combined with neural stem cell transplantation on hypoxic-ischemic encephalopathy are achieved by anti-inflammatory and an- ti-apoptotic mechanisms.展开更多
Lesions of the brainstem have been reported in the clinical scenarios of hypoxic-ischemic encephalopathy(HIE), although the prevalence of these lesions is probably underestimated. Neuropathologic studies have demonstr...Lesions of the brainstem have been reported in the clinical scenarios of hypoxic-ischemic encephalopathy(HIE), although the prevalence of these lesions is probably underestimated. Neuropathologic studies have demonstrated brainstem involvement in severely asphyxiated infants as an indicator of poor outcome. Among survivors to HIE, the most frequent clinical complaints that may be predicted by brainstem lesions include feeding problems, speech, language and communication problems and visual impairments. Clinical series, including vascular and metabolic etiologies, have found selective involvement of the brainstem with the demonstration of symmetric bilateral columnar lesions of the tegmentum. The role of brainstem lesions in HIE is currently a matter of debate, especially when tegmental lesions are present in the absence of supratentorial lesions. Differential diagnosis of tegmental lesions in neonates and infants include congenital metabolic syndromes and drug-related processes. Brainstem injury with the presence of supratentorial lesions is a predictor of poor outcome and high rates of mortality and morbidity. Further investigation will be conducted to identify specific sites of the brainstem that are vulnerable to hypoxic-ischemic and toxic-metabolic insults.展开更多
Although hypothermia therapy is effective to treat neonatal hypoxic-ischemic encephalopathy,many neonatal patients die or suffer from severe neurological dysfunction.Erythropoietin is considered one of the most promis...Although hypothermia therapy is effective to treat neonatal hypoxic-ischemic encephalopathy,many neonatal patients die or suffer from severe neurological dysfunction.Erythropoietin is considered one of the most promising neuroprotective agents.We hypothesized that erythropoietin combined with hypothermia will improve efficacy of neonatal hypoxic-ischemic encephalopathy treatment.In this study,41 neonates with moderate/severe hypoxic-ischemic encephalopathy were randomly divided into a control group（hypothermia alone for 72 hours,n = 20） and erythropoietin group（hypothermia ＋ erythropoietin 200 IU/kg for 10 days,n = 21）.Our results show that compared with the control group,serum tau protein levels were lower and neonatal behavioral neurological assessment scores higher in the erythropoietin group at 8 and 12 days.However,neurodevelopmental outcome was similar between the two groups at 9 months of age.These findings suggest that erythropoietin combined with hypothermia reduces serum tau protein levels and improves neonatal behavioral neurology outcome but does not affect long-term neurodevelopmental outcome.展开更多
It has been reported that early intervention of hyperbaric oxygen （HBO） can promote the intellectual rehabilitation of infants with severe hypoxic-ischemic encephalopathy （HIE） and can prevent mental retardation r...It has been reported that early intervention of hyperbaric oxygen （HBO） can promote the intellectual rehabilitation of infants with severe hypoxic-ischemic encephalopathy （HIE） and can prevent mental retardation recently. However, the prior observations on the therapeutic effect almost were short-term. How about the observations on prospective efficacy and the following up on systematic intelligence test？ OBJECTIVE： To investigate the short-term and long-term effects of HBO therapy on the promotion of the intellectual rehabilitation in infants with severe HIE. DESIGN： A comparative observation. SETTING： Department of Pediatrics, Affiliated Hospital, Qingdao University Medical College. PARTICIPANTS： Forty-seven infants with severe HIE （35 males and 12 females） were treated with HBO in the Department of Pediatrics, the Affiliated Hospital of the Medical College of Qingdao University from October 1996 to July 1999. All of them were consistent with the diagnostic criteria and clinical grading on severe HIE which were designed by Chinese Medical Association pediatrics committee neonate group in Hangzhou, October, 1996. Informed contents were obtained from the relatives of all the infants. METHODS： ① Grouping： The infants were randomly divided into two groups according to the order of admission, those of odd numbers were HBO group （n =24） and those of even numbers were control group （n =23）. All the infants were treated with routine therapy for 3 months, in addition to HBO therapy in the HBO group, once a day for 4 courses of l0 days with the interval of l0 - 15 days since 8 to l0 days after birth. HBO chamber produced by the 701 Institute of China Ship Industry Company was used, and the therapy pressure was 0.14- 0.16 MPa, and the time of compression and decompression were both 15 minutes while voltage-stabilizing was 30 minutes. ② In order to evaluate the short-term and long-term effects of HBO on intellectual rehabilitation in infants with HIE, neonatal behavioral neurological assessment （NBNA） was employed at 7 and 28 days after birth, and Bayley scale of infant development （BSID） was got at two years old in both groups, as well as Wechsler preschool and primary scale of intelligence （WPPSI） at five years. MAIN OUTCOME MEASURES： Comparison of short-term and long-term intelligence between the two groups. RESULTS： ① Results of NBNA： The NBNA score at 28 days was significantly higher in the HBO group than in the control group （P 〈 0.01）. ② Results of BSID： The score of mental development index （MDI） of BSID at two years old in the HBO group was significantly higher than that in the control group （P 〈 0.05）. ③ Results of WPPSI： The score of full-scale intelligence quotient （FIQ） and verbal intelligence quotient （VIQ） of WPPSI in the HBO group were significantly higher than those in the control group （P 〈 0.05）. In addition, the rate of mental retardation in the HBO group was significantly lower than that in the control group [12.5% （3/24）, 39.1%（9/23）, P 〈 0.05]. CONCLUSION： Not only the short-term intellectual rehabilitation but also the long-term one in infants with severe HIE could be promoted by HBO therapy, which might be benefit to the prevention of mental retardation.展开更多
Thioperamide, a selective histamine H3 receptor antagonist, can increase histamine content in the brain, improve brain edema, and exert a neuroprotective effect. This study aimed to examine the mechanism of action of ...Thioperamide, a selective histamine H3 receptor antagonist, can increase histamine content in the brain, improve brain edema, and exert a neuroprotective effect. This study aimed to examine the mechanism of action of thioperamide during brain edema in a rat model of neonatal hypoxic ischemic encephalopathy. Our results showed that thioperamide significantly decreased brain water content and malondialdehyde levels, while significantly increased histamine levels and superoxide dismutase activity in the hippocampus. This evidence demonstrates that thioperamide could pre vent oxidative damage and attenuate brain edema following neonatal hypoxicischemic encepha Iopathy. We further observed that changes in the above indexes occurred after combined treatment of thioperamide with the H1 receptor antagonist, pyrilamine, and the H2 receptor antagonist, ci metidine. Experimental findings indicated that pyrilamine reversed the effects of thioperamide; however, cimetidine had no significant influence on the effects of thioperamide. Our present findings suggest that thioperamide can increase brain histamine content and attenuate brain edema and oxidative damage by acting in combination with postsynaptic H1 receptors in a rat model of neo natal hypoxicischemic encephalopathy.展开更多
Hypoxic-ischemic encephalopathy（HIE） is a disease that occurs when the brain is subjected to hypoxia,resulting in neuronal death and neurological deficits,with a poor prognosis.The mechanisms underlying hypoxic-isch...Hypoxic-ischemic encephalopathy（HIE） is a disease that occurs when the brain is subjected to hypoxia,resulting in neuronal death and neurological deficits,with a poor prognosis.The mechanisms underlying hypoxic-ischemic brain injury include excitatory amino acid release,cellular proteolysis,reactive oxygen species generation,nitric oxide synthesis,and inflammation.The molecular and cellular changes in HIE include protein misfolding,aggregation,and destruction of organelles.The apoptotic pathways activated by ischemia and hypoxia include the mitochondrial pathway,the extrinsic Fas receptor pathway,and the endoplasmic reticulum stress-induced pathway.Numerous treatments for hypoxic-ischemic brain injury caused by HIE have been developed over the last half century.Hypothermia,xenon gas treatment,the use of melatonin and erythropoietin,and hypoxic-ischemic preconditioning have proven effective in HIE patients.Molecular chaperones are proteins ubiquitously present in both prokaryotes and eukaryotes.A large number of molecular chaperones are induced after brain ischemia and hypoxia,among which the heat shock proteins are the most important.Heat shock proteins not only maintain protein homeostasis; they also exert anti-apoptotic effects.Heat shock proteins maintain protein homeostasis by helping to transport proteins to their target destinations,assisting in the proper folding of newly synthesized polypeptides,regulating the degradation of misfolded proteins,inhibiting the aggregation of proteins,and by controlling the refolding of misfolded proteins.In addition,heat shock proteins exert anti-apoptotic effects by interacting with various signaling pathways to block the activation of downstream effectors in numerous apoptotic pathways,including the intrinsic pathway,the endoplasmic reticulum-stress mediated pathway and the extrinsic Fas receptor pathway.Molecular chaperones play a key role in neuroprotection in HIE.In this review,we provide an overview of the mechanisms of HIE and discuss the various treatment strategies.Given their critical role in the disease,molecular chaperones are promising therapeutic targets for HIE.展开更多
Introduction: Neonatal asphyxia is a major cause of infant morbidity in Cameroon. The aim of this study was to describe the short-term neurological outcome of children following neonatal Hypoxic-ischemic encephalopath...Introduction: Neonatal asphyxia is a major cause of infant morbidity in Cameroon. The aim of this study was to describe the short-term neurological outcome of children following neonatal Hypoxic-ischemic encephalopathy (HIE). Methodology: We conducted a retrospective cohort study from May 2010 to September 2013. We included 39 exposed cases against 78 non-exposed cases followed-up for at least 9 months. The variables studied were: age, sex, head circumference, neurological sequelae, postural anomalies and motor skills and developmental age/quotient. The data collected were analyzed using Epi info software version 3.5.3. The Fisher Exact Test was used to compare the variables with a significance threshold defined for p Results: We recruited 39 cases for 78 controls. The majority (74.40%) of cases were classified as HIE Sarnat 3 and 25.60% Sarnat 2. Most of the children were aged 12 - 36 months with a mean age of 18 months. The male sex was predominant with a sex ratio of 1.2;and 61.50% of children with HIE had head circumference Conclusion: The frequency of neurological sequelae following HIE was high in our series. Efforts should be made to prevent perinatal asphyxia and to ensure the availability of material and staff trained to help babies’ breath in all the delivery rooms in our maternities.展开更多
Objective To study the changes of the nitric oxide(NO) in process of neonate hypoxic－ ischemic encephalopathy(HIE) and the relations between the concentrations of NO and HIE. Methods Tested the concentrations of NO i...Objective To study the changes of the nitric oxide(NO) in process of neonate hypoxic－ ischemic encephalopathy(HIE) and the relations between the concentrations of NO and HIE. Methods Tested the concentrations of NO in CSF of newborn infants suffered HIE the third day and in plasma of newborn infants suffered HIE just attacked instant(within 2 hours), the first day ,the third day and restoring stage and compared with them of normal contrast term. We tried to analyse the reasons and significance of NO change .Results The NO concentration is the highest in plasma of newborn infants suffered HIE the first day. There is significant difference(P<0.01) after comparing the NO concentrations in plasmas of newborn infants suffered HIE just attacked instant, the first day, the third day with of normal contrast team respectively. But there is not significant difference(P >0.05) between NO in plasmas of restoring stage and of normal contrast team. There is positive correlation between the NO concentration in plasma and in CSF of newborn infants suffered HIE the third day. The more serious the disease is, the higher the NO concentration is, the worse the prognosis is. Conclusion NO play along with the course of HIE and play an important role in neonate HIE. Testing the concentration of NO in plasma and in CSF can also help to judge the degree of disease.展开更多
Objective:To explore the effects of mild hypothermia combined EPO therapy on cerebral injury, myocardial injury and oxidative stress of neonatal hypoxic ischemic encephalopathy. Methods: A total of 72 children with HI...Objective:To explore the effects of mild hypothermia combined EPO therapy on cerebral injury, myocardial injury and oxidative stress of neonatal hypoxic ischemic encephalopathy. Methods: A total of 72 children with HIE who were diagnosed and treated in the hospital between December 2015 and June 2017 were chosen as the study subjects and divided into control group (n=36) and EPO group (n=36) by random number table method. Control group received mild hypothermia therapy on the basis of conventional therapy, and EPO group received EPO therapy on the basis of the therapy for control group. The differences in serum levels of cerebral injury indexes, myocardial injury indexes and oxidative stress indexes were compared between the two groups before and after treatment.Results: The differences in serum levels of cerebral injury indexes, myocardial injury indexes and oxidative stress indexes were not statistically significant between the two groups before treatment. After the treatment ended, serum cerebral injury indexes VILIP-1, NPY and NSE levels of EPO group were lower than those of control group whereas IGF-1 level was higher than that of control group;myocardial injury indexes CT-1, Myo and cTnⅠ levels were lower than those of control group;oxidative stress indexes GSH-Px and SOD levels were higher than those of control group whereas AOPP and ROS levels were lower than those of control group.Conclusion: Mild hypothermia combined with EPO therapy can improve the cerebral injury, myocardial injury and oxidative stress of neonatal hypoxic ischemic encephalopathy.展开更多
Objective:To study the evaluation value of the quantitative electroencephalogram (qEEG) for the prognosis of neonatal hypoxic ischemic encephalopathy (HIE) and its relationship with serological indicators.Methods: 76 ...Objective:To study the evaluation value of the quantitative electroencephalogram (qEEG) for the prognosis of neonatal hypoxic ischemic encephalopathy (HIE) and its relationship with serological indicators.Methods: 76 children with HIE who were born and treated in our hospital between April 2013 and February 2017 were collected as observation group, and 50 healthy newborns who were born in our hospital during the same period were collected as normal control group. qEEG parameter values of two groups of children were determined, serum levels of nerve injury indexes, nerve apoptosis indexes and oxidative stress indexes were compared between the two groups, and Pearson test was used to evaluate the inner link between qEEG parameter values and disease severity in children with HIE.Results: qEEG Fp1, Fp2, C3, C4, T3, T4, O1 and O2 loci power spectrum values of observation group were significantly lower than those of normal control group. Serum NSE, NPY, S-100B and MBP contents in observation group were higher than those in normal control group;nerve apoptosis indexes sFas, sFasL and Caspase-3 contents were higher than those in normal control group while Bcl-2 content was lower than that in normal control group;serum oxidative stress indexes AOPP and MDA contents were higher than those in normal control group while SOD content was lower than that in normal control group. Pearson test showed that qEEG Fp1, Fp2, C3, C4, T3, T4, O1 and O2 loci power spectrum values in children with HIE were directly correlated with the contents of nerve injury indexes, nerve apoptosis indexes and oxidative stress indexes. Conclusion: The qEEG parameter values in children with HIE are lower than those in normal children, and the specific values are closely related to the severity of the disease.展开更多
Perinatal hypoxic-ischemic-encephalopathy significantly contributes to neonatal death and life-long disability such as cerebral palsy. Advances in signal processing and machine learning have provided the research comm...Perinatal hypoxic-ischemic-encephalopathy significantly contributes to neonatal death and life-long disability such as cerebral palsy. Advances in signal processing and machine learning have provided the research community with an opportunity to develop automated real-time identification techniques to detect the signs of hypoxic-ischemic-encephalopathy in larger electroencephalography/amplitude-integrated electroencephalography data sets more easily. This review details the recent achievements, performed by a number of prominent research groups across the world, in the automatic identification and classification of hypoxic-ischemic epileptiform neonatal seizures using advanced signal processing and machine learning techniques. This review also addresses the clinical challenges that current automated techniques face in order to be fully utilized by clinicians, and highlights the importance of upgrading the current clinical bedside sampling frequencies to higher sampling rates in order to provide better hypoxic-ischemic biomarker detection frameworks. Additionally, the article highlights that current clinical automated epileptiform detection strategies for human neonates have been only concerned with seizure detection after the therapeutic latent phase of injury. Whereas recent animal studies have demonstrated that the latent phase of opportunity is critically important for early diagnosis of hypoxic-ischemic-encephalopathy electroencephalography biomarkers and although difficult, detection strategies could utilize biomarkers in the latent phase to also predict the onset of future seizures.展开更多
基金supported by the Jiangsu Maternal and Child Health Research Project of China,No.F201612(to HXL)Changzhou Science and Technology Support Plan of China,No.CE20165027(to HXL)+1 种基金Changzhou City Planning Commission Major Science and Technology Projects of China,No.ZD201515(to HXL)Changzhou High Level Training Fund for Health Professionals of China,No.2016CZBJ028(to HXL)
文摘Resting-state functional magnetic resonance imaging has revealed disrupted brain network connectivity in adults and teenagers with cerebral palsy. However, the specific brain networks implicated in neonatal cases remain poorly understood. In this study, we recruited 14 termborn infants with mild hypoxic ischemic encephalopathy and 14 term-born infants with severe hypoxic ischemic encephalopathy from Changzhou Children's Hospital, China. Resting-state functional magnetic resonance imaging data showed efficient small-world organization in whole-brain networks in both the mild and severe hypoxic ischemic encephalopathy groups. However, compared with the mild hypoxic ischemic encephalopathy group, the severe hypoxic ischemic encephalopathy group exhibited decreased local efficiency and a low clustering coefficient. The distribution of hub regions in the functional networks had fewer nodes in the severe hypoxic ischemic encephalopathy group compared with the mild hypoxic ischemic encephalopathy group. Moreover, nodal efficiency was reduced in the left rolandic operculum, left supramarginal gyrus, bilateral superior temporal gyrus, and right middle temporal gyrus. These results suggest that the topological structure of the resting state functional network in children with severe hypoxic ischemic encephalopathy is clearly distinct from that in children with mild hypoxic ischemic encephalopathy, and may be associated with impaired language, motion, and cognition. These data indicate that it may be possible to make early predictions regarding brain development in children with severe hypoxic ischemic encephalopathy, enabling early interventions targeting brain function. This study was approved by the Regional Ethics Review Boards of the Changzhou Children's Hospital(approval No. 2013-001) on January 31, 2013. Informed consent was obtained from the family members of the children. The trial was registered with the Chinese Clinical Trial Registry(registration number: ChiCTR1800016409) and the protocol version is 1.0.
基金supported by The Health Research Council of New Zealand(grant No.16/003,17/601)the Marsden Fund(grant No.17-UOA232)a Sir Charles Hercus Fellowship from the Health Research Council of New Zealand(grant No.16/003)
文摘Perinatal hypoxic-ischemic encephalopathy is a leading cause of neonatal death and disability.Therapeutic hypothermia significantly reduces death and major disability associated with hypoxic-ischemic encephalopathy;however,many infants still experience lifelong disabilities to movement,sensation and cognition.Clinical guidelines,based on strong clinical and preclinical evidence,recommend therapeutic hypothermia should be started within 6 hours of birth and continued for a period of 72 hours,with a target brain temperature of 33.5 ±0.5℃ for infants with moderate to severe hypoxic-ischemic encephalopathy.The clinical guidelines also recommend that infants be re warmed at a rate of 0.5℃ per hour,but this is not based on strong evidence.There are no randomized controlled trials investigating the optimal rate of rewarming after therapeutic hypothermia for infants with hypoxic-ischemic encephalopathy.Preclinical studies of rewarming are conflicting and results were confounded by treatment with sub-optimal durations of hypothermia.In this review,we evaluate the evidence for the optimal start time,duration and depth of hypothermia,and whether the rate of rewarming after treatment affects brain injury and neurological outcomes.
基金supported by the National Natural Science Foundation of China,No.81271382
文摘Neural stem cell transplantation is a useful treatment for ischemic stroke, but apoptosis often occurs in the hypoxic-ischemic environment of the brain after cell transplantation. In this study, we determined if mild hypothermia （27-28~C） can increase the survival rate of neural stem cells （1.0 x 105/~tL） transplanted into neonatal mice with hypoxic-ischemic encephalopathy. Long-term effects on neurological functioning of the mice were also examined. After mild hy- pothermia combined with neural stem cell transplantation, we observed decreased expression levels of inflammatory factor nuclear factor-kappa B and apoptotic factor caspase-3, reduced cerebral infarct volumes, increased survival rate of transplanted cells, and marked improvements in neurological function. Thus, the neuroprotective effects of mild hypothermia combined with neural stem cell transplantation are superior to those of monotherapy. Moreover, our findings suggest that the neuroprotective effects of mild hypothermia combined with neural stem cell transplantation on hypoxic-ischemic encephalopathy are achieved by anti-inflammatory and an- ti-apoptotic mechanisms.
文摘Lesions of the brainstem have been reported in the clinical scenarios of hypoxic-ischemic encephalopathy(HIE), although the prevalence of these lesions is probably underestimated. Neuropathologic studies have demonstrated brainstem involvement in severely asphyxiated infants as an indicator of poor outcome. Among survivors to HIE, the most frequent clinical complaints that may be predicted by brainstem lesions include feeding problems, speech, language and communication problems and visual impairments. Clinical series, including vascular and metabolic etiologies, have found selective involvement of the brainstem with the demonstration of symmetric bilateral columnar lesions of the tegmentum. The role of brainstem lesions in HIE is currently a matter of debate, especially when tegmental lesions are present in the absence of supratentorial lesions. Differential diagnosis of tegmental lesions in neonates and infants include congenital metabolic syndromes and drug-related processes. Brainstem injury with the presence of supratentorial lesions is a predictor of poor outcome and high rates of mortality and morbidity. Further investigation will be conducted to identify specific sites of the brainstem that are vulnerable to hypoxic-ischemic and toxic-metabolic insults.
基金supported by a grant from the Health and Family Planning Commission of Hebei Province of China,No.20150033a grant from the Science and Technology Research and Development Project of Handan City of Hebei Province of China,No.152810879-6
文摘Although hypothermia therapy is effective to treat neonatal hypoxic-ischemic encephalopathy,many neonatal patients die or suffer from severe neurological dysfunction.Erythropoietin is considered one of the most promising neuroprotective agents.We hypothesized that erythropoietin combined with hypothermia will improve efficacy of neonatal hypoxic-ischemic encephalopathy treatment.In this study,41 neonates with moderate/severe hypoxic-ischemic encephalopathy were randomly divided into a control group（hypothermia alone for 72 hours,n = 20） and erythropoietin group（hypothermia ＋ erythropoietin 200 IU/kg for 10 days,n = 21）.Our results show that compared with the control group,serum tau protein levels were lower and neonatal behavioral neurological assessment scores higher in the erythropoietin group at 8 and 12 days.However,neurodevelopmental outcome was similar between the two groups at 9 months of age.These findings suggest that erythropoietin combined with hypothermia reduces serum tau protein levels and improves neonatal behavioral neurology outcome but does not affect long-term neurodevelopmental outcome.
文摘It has been reported that early intervention of hyperbaric oxygen （HBO） can promote the intellectual rehabilitation of infants with severe hypoxic-ischemic encephalopathy （HIE） and can prevent mental retardation recently. However, the prior observations on the therapeutic effect almost were short-term. How about the observations on prospective efficacy and the following up on systematic intelligence test？ OBJECTIVE： To investigate the short-term and long-term effects of HBO therapy on the promotion of the intellectual rehabilitation in infants with severe HIE. DESIGN： A comparative observation. SETTING： Department of Pediatrics, Affiliated Hospital, Qingdao University Medical College. PARTICIPANTS： Forty-seven infants with severe HIE （35 males and 12 females） were treated with HBO in the Department of Pediatrics, the Affiliated Hospital of the Medical College of Qingdao University from October 1996 to July 1999. All of them were consistent with the diagnostic criteria and clinical grading on severe HIE which were designed by Chinese Medical Association pediatrics committee neonate group in Hangzhou, October, 1996. Informed contents were obtained from the relatives of all the infants. METHODS： ① Grouping： The infants were randomly divided into two groups according to the order of admission, those of odd numbers were HBO group （n =24） and those of even numbers were control group （n =23）. All the infants were treated with routine therapy for 3 months, in addition to HBO therapy in the HBO group, once a day for 4 courses of l0 days with the interval of l0 - 15 days since 8 to l0 days after birth. HBO chamber produced by the 701 Institute of China Ship Industry Company was used, and the therapy pressure was 0.14- 0.16 MPa, and the time of compression and decompression were both 15 minutes while voltage-stabilizing was 30 minutes. ② In order to evaluate the short-term and long-term effects of HBO on intellectual rehabilitation in infants with HIE, neonatal behavioral neurological assessment （NBNA） was employed at 7 and 28 days after birth, and Bayley scale of infant development （BSID） was got at two years old in both groups, as well as Wechsler preschool and primary scale of intelligence （WPPSI） at five years. MAIN OUTCOME MEASURES： Comparison of short-term and long-term intelligence between the two groups. RESULTS： ① Results of NBNA： The NBNA score at 28 days was significantly higher in the HBO group than in the control group （P 〈 0.01）. ② Results of BSID： The score of mental development index （MDI） of BSID at two years old in the HBO group was significantly higher than that in the control group （P 〈 0.05）. ③ Results of WPPSI： The score of full-scale intelligence quotient （FIQ） and verbal intelligence quotient （VIQ） of WPPSI in the HBO group were significantly higher than those in the control group （P 〈 0.05）. In addition, the rate of mental retardation in the HBO group was significantly lower than that in the control group [12.5% （3/24）, 39.1%（9/23）, P 〈 0.05]. CONCLUSION： Not only the short-term intellectual rehabilitation but also the long-term one in infants with severe HIE could be promoted by HBO therapy, which might be benefit to the prevention of mental retardation.
基金supported by Jilin Provincial Science and Technology Department Foundation ofChina, No. 200905134
文摘Thioperamide, a selective histamine H3 receptor antagonist, can increase histamine content in the brain, improve brain edema, and exert a neuroprotective effect. This study aimed to examine the mechanism of action of thioperamide during brain edema in a rat model of neonatal hypoxic ischemic encephalopathy. Our results showed that thioperamide significantly decreased brain water content and malondialdehyde levels, while significantly increased histamine levels and superoxide dismutase activity in the hippocampus. This evidence demonstrates that thioperamide could pre vent oxidative damage and attenuate brain edema following neonatal hypoxicischemic encepha Iopathy. We further observed that changes in the above indexes occurred after combined treatment of thioperamide with the H1 receptor antagonist, pyrilamine, and the H2 receptor antagonist, ci metidine. Experimental findings indicated that pyrilamine reversed the effects of thioperamide; however, cimetidine had no significant influence on the effects of thioperamide. Our present findings suggest that thioperamide can increase brain histamine content and attenuate brain edema and oxidative damage by acting in combination with postsynaptic H1 receptors in a rat model of neo natal hypoxicischemic encephalopathy.
文摘Hypoxic-ischemic encephalopathy（HIE） is a disease that occurs when the brain is subjected to hypoxia,resulting in neuronal death and neurological deficits,with a poor prognosis.The mechanisms underlying hypoxic-ischemic brain injury include excitatory amino acid release,cellular proteolysis,reactive oxygen species generation,nitric oxide synthesis,and inflammation.The molecular and cellular changes in HIE include protein misfolding,aggregation,and destruction of organelles.The apoptotic pathways activated by ischemia and hypoxia include the mitochondrial pathway,the extrinsic Fas receptor pathway,and the endoplasmic reticulum stress-induced pathway.Numerous treatments for hypoxic-ischemic brain injury caused by HIE have been developed over the last half century.Hypothermia,xenon gas treatment,the use of melatonin and erythropoietin,and hypoxic-ischemic preconditioning have proven effective in HIE patients.Molecular chaperones are proteins ubiquitously present in both prokaryotes and eukaryotes.A large number of molecular chaperones are induced after brain ischemia and hypoxia,among which the heat shock proteins are the most important.Heat shock proteins not only maintain protein homeostasis; they also exert anti-apoptotic effects.Heat shock proteins maintain protein homeostasis by helping to transport proteins to their target destinations,assisting in the proper folding of newly synthesized polypeptides,regulating the degradation of misfolded proteins,inhibiting the aggregation of proteins,and by controlling the refolding of misfolded proteins.In addition,heat shock proteins exert anti-apoptotic effects by interacting with various signaling pathways to block the activation of downstream effectors in numerous apoptotic pathways,including the intrinsic pathway,the endoplasmic reticulum-stress mediated pathway and the extrinsic Fas receptor pathway.Molecular chaperones play a key role in neuroprotection in HIE.In this review,we provide an overview of the mechanisms of HIE and discuss the various treatment strategies.Given their critical role in the disease,molecular chaperones are promising therapeutic targets for HIE.
文摘Introduction: Neonatal asphyxia is a major cause of infant morbidity in Cameroon. The aim of this study was to describe the short-term neurological outcome of children following neonatal Hypoxic-ischemic encephalopathy (HIE). Methodology: We conducted a retrospective cohort study from May 2010 to September 2013. We included 39 exposed cases against 78 non-exposed cases followed-up for at least 9 months. The variables studied were: age, sex, head circumference, neurological sequelae, postural anomalies and motor skills and developmental age/quotient. The data collected were analyzed using Epi info software version 3.5.3. The Fisher Exact Test was used to compare the variables with a significance threshold defined for p Results: We recruited 39 cases for 78 controls. The majority (74.40%) of cases were classified as HIE Sarnat 3 and 25.60% Sarnat 2. Most of the children were aged 12 - 36 months with a mean age of 18 months. The male sex was predominant with a sex ratio of 1.2;and 61.50% of children with HIE had head circumference Conclusion: The frequency of neurological sequelae following HIE was high in our series. Efforts should be made to prevent perinatal asphyxia and to ensure the availability of material and staff trained to help babies’ breath in all the delivery rooms in our maternities.
基金Foundation:Guangdong province board of health item (number 199906)
文摘Objective To study the changes of the nitric oxide(NO) in process of neonate hypoxic－ ischemic encephalopathy(HIE) and the relations between the concentrations of NO and HIE. Methods Tested the concentrations of NO in CSF of newborn infants suffered HIE the third day and in plasma of newborn infants suffered HIE just attacked instant(within 2 hours), the first day ,the third day and restoring stage and compared with them of normal contrast term. We tried to analyse the reasons and significance of NO change .Results The NO concentration is the highest in plasma of newborn infants suffered HIE the first day. There is significant difference(P<0.01) after comparing the NO concentrations in plasmas of newborn infants suffered HIE just attacked instant, the first day, the third day with of normal contrast team respectively. But there is not significant difference(P >0.05) between NO in plasmas of restoring stage and of normal contrast team. There is positive correlation between the NO concentration in plasma and in CSF of newborn infants suffered HIE the third day. The more serious the disease is, the higher the NO concentration is, the worse the prognosis is. Conclusion NO play along with the course of HIE and play an important role in neonate HIE. Testing the concentration of NO in plasma and in CSF can also help to judge the degree of disease.
文摘Objective:To explore the effects of mild hypothermia combined EPO therapy on cerebral injury, myocardial injury and oxidative stress of neonatal hypoxic ischemic encephalopathy. Methods: A total of 72 children with HIE who were diagnosed and treated in the hospital between December 2015 and June 2017 were chosen as the study subjects and divided into control group (n=36) and EPO group (n=36) by random number table method. Control group received mild hypothermia therapy on the basis of conventional therapy, and EPO group received EPO therapy on the basis of the therapy for control group. The differences in serum levels of cerebral injury indexes, myocardial injury indexes and oxidative stress indexes were compared between the two groups before and after treatment.Results: The differences in serum levels of cerebral injury indexes, myocardial injury indexes and oxidative stress indexes were not statistically significant between the two groups before treatment. After the treatment ended, serum cerebral injury indexes VILIP-1, NPY and NSE levels of EPO group were lower than those of control group whereas IGF-1 level was higher than that of control group;myocardial injury indexes CT-1, Myo and cTnⅠ levels were lower than those of control group;oxidative stress indexes GSH-Px and SOD levels were higher than those of control group whereas AOPP and ROS levels were lower than those of control group.Conclusion: Mild hypothermia combined with EPO therapy can improve the cerebral injury, myocardial injury and oxidative stress of neonatal hypoxic ischemic encephalopathy.
文摘Objective:To study the evaluation value of the quantitative electroencephalogram (qEEG) for the prognosis of neonatal hypoxic ischemic encephalopathy (HIE) and its relationship with serological indicators.Methods: 76 children with HIE who were born and treated in our hospital between April 2013 and February 2017 were collected as observation group, and 50 healthy newborns who were born in our hospital during the same period were collected as normal control group. qEEG parameter values of two groups of children were determined, serum levels of nerve injury indexes, nerve apoptosis indexes and oxidative stress indexes were compared between the two groups, and Pearson test was used to evaluate the inner link between qEEG parameter values and disease severity in children with HIE.Results: qEEG Fp1, Fp2, C3, C4, T3, T4, O1 and O2 loci power spectrum values of observation group were significantly lower than those of normal control group. Serum NSE, NPY, S-100B and MBP contents in observation group were higher than those in normal control group;nerve apoptosis indexes sFas, sFasL and Caspase-3 contents were higher than those in normal control group while Bcl-2 content was lower than that in normal control group;serum oxidative stress indexes AOPP and MDA contents were higher than those in normal control group while SOD content was lower than that in normal control group. Pearson test showed that qEEG Fp1, Fp2, C3, C4, T3, T4, O1 and O2 loci power spectrum values in children with HIE were directly correlated with the contents of nerve injury indexes, nerve apoptosis indexes and oxidative stress indexes. Conclusion: The qEEG parameter values in children with HIE are lower than those in normal children, and the specific values are closely related to the severity of the disease.
基金supported by the Auckland Medical Research Foundation,No.1117017(to CPU)
文摘Perinatal hypoxic-ischemic-encephalopathy significantly contributes to neonatal death and life-long disability such as cerebral palsy. Advances in signal processing and machine learning have provided the research community with an opportunity to develop automated real-time identification techniques to detect the signs of hypoxic-ischemic-encephalopathy in larger electroencephalography/amplitude-integrated electroencephalography data sets more easily. This review details the recent achievements, performed by a number of prominent research groups across the world, in the automatic identification and classification of hypoxic-ischemic epileptiform neonatal seizures using advanced signal processing and machine learning techniques. This review also addresses the clinical challenges that current automated techniques face in order to be fully utilized by clinicians, and highlights the importance of upgrading the current clinical bedside sampling frequencies to higher sampling rates in order to provide better hypoxic-ischemic biomarker detection frameworks. Additionally, the article highlights that current clinical automated epileptiform detection strategies for human neonates have been only concerned with seizure detection after the therapeutic latent phase of injury. Whereas recent animal studies have demonstrated that the latent phase of opportunity is critically important for early diagnosis of hypoxic-ischemic-encephalopathy electroencephalography biomarkers and although difficult, detection strategies could utilize biomarkers in the latent phase to also predict the onset of future seizures.
